1. Field of the Invention
The present invention relates, generally, to medical testing apparatus and methods. More particularly, the invention relates to an iontophoreses device for evoking and measuring a sweat response. The invention has particular utility in measuring the rate and volume of the evoked sweat output for studies of a patient's autonomic nervous system.
2. Background Information
The state of the art includes various devices and methods for evoking and capturing a sweat sample.
Such samples are particularly useful, for instance, in the diagnosis of cystic fibrosis (CF). Cystic fibrosis is one of the most common genetic diseases among Caucasians and is a contributing factor in causing suffering among children and adults. CF affects the mucus-producing glands and other exocrine glands in the body. Clinically, CF is characterized by chronic respiratory infections and obstructive lung disease, pancreatic gland insufficiency leading to an inability to digest fats, male infertility and abnormally high levels of electrolytes in the sweat.
The sweat gland defect in CF has been well characterized for years and is presently used to help diagnose CF, by the use of a "pilocarpine iontophroesis sweat test". Sweat production is stimulated through two pathways: the cholinergic pathway and by the adrenergic/sympathetic pathway (i.e., fight or flight response). Thus, sweat production can be stimulated by both cholinergic and adrenergic agonists. It is the collection of cholinergic stimulated sweat, using the cholinergic agonist pilocarpine, and the subsequent measurement of sweat chloride concentration, that forms the basis of standard diagnostic testing for cystic fibrosis (CF).
Samples of sweat may be collected in various ways. The most common method used today is to introduce pilocarpine nitrate into the skin by iontophoresis, a process in which an electrical current is delivered through the skin between a pair of electrodes attached to the skin. Generally, current flow is continued for about 15 minutes, after which the electrodes arc removed and a collection cup is placed over the area of the skin where the pilocarpine nitrate has been administered. After approximately 15 minutes, the sweat that has formed on the skin under the cup is collected into the cup by scraping the cup across the skin. Normally the collection cup is at room temperature, which is a temperature below normal body and skin temperature.
Stimulation of sweat production with pilocarpine leads to initial production of an isotonic secretion in the sweat gland. In non-CF patients, as the secretion traverses the sweat duct, chloride is reabsorbed. This leads to low concentration of chloride in sweat as it appears on the skin. This chloride resorption is dependent on the presence of a functional CF related gene (known as "CFTR"). In CF patients, who lack functional CFTR, the sweat chloride concentration remains high, and distinguishes most, but not all, CF from non-CF patients. However, this technique does not distinguish heterozygote carriers of CFTR mutations from non carriers, nor does the sweat chloride concentration correlate with disease severity. Furthermore, the pilocarpine test involves the use of a sweat test apparatus consisting of electrodes and a voltage source and the use of specially trained personnel. These methods require the elution of the sweat electrolytes collected on the pads and determination of chloride content of the sweat. While this method remains the "gold standard", it occasionally yields ambiguous results. Therefore, it would be useful to have an alternative or better method of diagnosing CF.
In one approach, U.S. Pat. No. 4,266,556 (Barlow, et al. May 12, 1981) describes a sweat collection device for use with equipment for inducing sweat has a cup member that is electrically heated and in which the temperature of the cup is maintained substantially constant by temperature monitoring and controlling supply of electrical power to the cup in accordance with the requirements determined by the temperature monitoring.
In another approach, U.S. Pat. No. 4,398,543 (Sandlin, et al. Aug. 16, 1983) describes a moisture collecting chamber having a probe which engages the skin to form a seal between the probe and the skin surface which is being tested and to provide a substantially uniform force when the probe is positioned on a patient. A connecting mechanism is attached to the probe and limiting means is mounted with the probe to provide uniform pressure of the probe against the skin surface during each test.
Various other sweat test devices have been described or arc in current use. For instance, Abrams Instrument Corporation markets a device known as the "Abrams Model WVD-101 Evaporative Water Loss Instrument". The Abrams device is a "single channel" system that uses an air-perfuse capsule, sealed to the skin surface, to measures the rate of water evaporation from that surface.
Yet other known devices or approaches include, the Wescor Sweat Check Conductivity Analyzer which employs iontophoresis using a pilocarpine gel disc to evoke sweat and collects the sweat in a concave chamber to be examined or tested. See also the Chloride Test Patch System from Medtronic, which employs iontophoresis using a pilocarpine interface pad to evoke sweat. A test patch is placed over the area of seating to collect and analyze the sample for chloride concentration. While each such device typically uses iontophoresis to evoke a sweat response, and measures at least one characteristic or parameter of the sweat evoked, they tend to differ in several respects as well, including the fact that they generally do not permit the measurement of both the rate and volume of sweat produced. Rather, they tend to concentrate on the concentration of sodium in the sweat itself, in their relatively limited roles as a screening tools for CF. Nor do they tend to provide either a chamber to contain moisture vapor upon the skin, or in turn, one or more sensors to measure corresponding parameters within the chamber, while in its position upon the skin.
Generally, quantitative sudomotor axon reflex testing methods have been previously described and have well accepted roles in medical diagnosis. See, for instance, Low, PA, et al., "Standardization of Autonomic Function", Chapter 23, pp. 287-295 in Clinical Autonomic Disorders, 2.sup.nd, ed. Lippincott-Raven Publishers (1997). It appears to be the corresponding apparatuses themselves that are in need of improvement.
The devices and methods of the known art are believed to have significant limitations and shortcomings. Specifically, the devices and methods of the known art use a bottle of pressurized nitrogen gas or another pressurized gas source as a dry vapor source. Additionally, the devices and methods of the known art do not have the small and compact sensors positioned in the skin capsule, including temperature and humidity sensors, mass airflow sensors, a humidity sensor, and an absolute pressure sensor. The devices and methods of the known art also lacked a voltage sensitive orifice within the main enclosure of the device to control and prepare the dry air for circulation out to the collection capsule affixed on the skin. Furthermore, known sweat testing devices lack a donut-shaped stimulating agent gel that snaps onto the sweat sample collection capsule to evoke sweat for purposes of measuring resting and evoked moisture emission.
The present invention provides an apparatus and method for evoking and capturing a sweat sample which is believed to constitute an improvement over the known art.